EP0105574B1 - Schwimmender Magnetrührer für Kulturen - Google Patents

Schwimmender Magnetrührer für Kulturen Download PDF

Info

Publication number
EP0105574B1
EP0105574B1 EP83303260A EP83303260A EP0105574B1 EP 0105574 B1 EP0105574 B1 EP 0105574B1 EP 83303260 A EP83303260 A EP 83303260A EP 83303260 A EP83303260 A EP 83303260A EP 0105574 B1 EP0105574 B1 EP 0105574B1
Authority
EP
European Patent Office
Prior art keywords
flask
stirrer
liquid
liquid medium
magnet
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
EP83303260A
Other languages
English (en)
French (fr)
Other versions
EP0105574A2 (de
EP0105574A3 (en
Inventor
Norman A. De Bruyne
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Techne Inc
Original Assignee
Techne Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Techne Inc filed Critical Techne Inc
Publication of EP0105574A2 publication Critical patent/EP0105574A2/de
Publication of EP0105574A3 publication Critical patent/EP0105574A3/en
Application granted granted Critical
Publication of EP0105574B1 publication Critical patent/EP0105574B1/de
Expired legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/08—Flask, bottle or test tube
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/45—Magnetic mixers; Mixers with magnetically driven stirrers
    • B01F33/452—Magnetic mixers; Mixers with magnetically driven stirrers using independent floating stirring elements
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/50—Means for positioning or orientating the apparatus
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/56—Floating elements
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
    • C12M27/02—Stirrer or mobile mixing elements

Definitions

  • the present invention relates to stirrers, and stirring methods, wherein a magnetically attractable stirrer element floats in a body of liquid and is caused to move by a rotating magnetic field.
  • Apparatus for stirring liquid materials, including culture mediums have long been known, particularly stirrer apparatus in which a motor, within a housing, is used to rotate a magnet beneath a platform formed on the housing. On the platform, there is a flask having liquid, such as liquid culture medium in it, and a magnet is positioned in the liquid culture medium, and is caused to rotate by the motor-driven magnet in the housing, due to magnetic coupling between the driving magnet and the driven magnet.
  • These magnetic stirrers may generally be classified into two types.
  • a first type has a cap or top on the flask or other vessel, and the driven magnet is supported by or from this cap or top.
  • Examples of such top- supported driven magnets are as follows. Jacobs, U.S. Patent No. 2,932,493 discloses a stirrer in which the driven magnet is suspended from the top by a chain or a rod, and is positioned sightly above the bottom of the vessel. Harker, U.S. Patent No. 3,572,651, provides a flask for stirring a suspension culture of cells in a medium of nutrient substances, includes a magnet supported by a shaft, the shaft being held by. a bearing supported by the top or cap of the vessel.
  • Mazowski U.S. Patent No.
  • a second type of magnetic stirrer apparatus has the driven magnet supported by the bottom of the vessel in which the liqud is contained.
  • Hendricks U.S. Patent No. 2,459,224, discloses a stirrer apparatus which includes a magnet at the lower end of a shaft, which rests on the bottom of a container, the shaft having a disc-type agitator fixed to it; rotation of the magnet causes rotation of the shaft and agitator.
  • Steel, U.S. Patent No. 3,245,665 provides a mixing bar which includes an encapsulating body having a pair of permanent bar magnets embodied in it, and intended to rest on the bottom of a flask and to be rotated by a suitable driven magnet.
  • Bender U.S. Patent No. 4,162,855, includes a magnetic rotor mounted within a positioning cage which positions the rotor at the bottom of the vessel; the cage is provided with bearings for rotatably supporting a magnet.
  • Microcarriers are tiny solid beads, which are added in large numbers to the nutrient liquid medium, thereby to increase the surface area in the flask, this technique being used in the cultivation of so-called “anchorage dependent cells" which require large areas of solid surface.
  • the noted article also discloses the construction of a flask, known as the Pearson flask, which is characterized by a small conical projection located centrally in the bottom wall of the flask or vessel, which is used in combination with a stirrer suspended from a bearing on the underside of the top or cap of the vessel, on the same axis as the conical projection, the lower end of the stirrer being bulbous and extending into the trough formed between the conical projection and the vertical, cylindrical walls of the flask.
  • the Pearson flask has been found to give the above noted secondary circulation, thereby providing, by definition, vertical motion of the particles, with enhanced culture activity.
  • a method of stirring a liquid medium characterized by placing said medium in a flask by placing in said flask a stirrer comprising a bouyant bar magnet, by placing the flask with the liquid stirrer therein in juxtaposition with means for generating a rotatable magnetic field so that the permanent magnet is in said field, and by energizing said rotatable field generating means to thereby rotate said stirrer, which has a density less than that of the liquid medium.
  • the stirrer therefore floats in the liquid, and is at the liquid-gas (air) interface.
  • the flask is a Pearson flask, having a conical projection located centrally in the bottom, to provide enhanced secondary motion or flow.
  • the bouyant stirrer may be a cylinder of suitable heat-resistant material, sealed at its ends, and containing one or more bar magnets.
  • Alternate constructions may include buoyant magnetic stirrers with bulbous end portions either joined together, or held in spaced relation by a connecting linear portion of greater or lesser length, depending upon the size of the flask in which the stirrer is to be placed. In these latter constructions, one or more bar magnets are also placed, extending between two bulbous end portions, and, possibly, into them.
  • a cylinder of magnetic material having closed ends, and a density less than the density of the liquid medium, so that it will float therein.
  • the floating stirrer in whatever form, has a density approximately one-half of the density of the liquid in which it is placed.
  • the materials for utility are able to withstand wet steam of high temperature, such as 123°C.
  • the invention also encompasses a system as claimed in claim 7 for carrying out the claimed method and a stirrer as claimed in claim 11 or 16.
  • the buoyant stirrer may be provided with an impeller positioned to cause or enhance secondary motion or flow of the liquid.
  • the impeller comprises blades, preferably supported beneath the buoyancy chamber and inclined to cause upward movement as the buoyant magnetic stirrer is rotated by the rotating magnetic field.
  • the herein disclosed method includes the provision of a medium in a flask, and the introduction of a buoyant magnetic stirrer, followed by rotation of the stirrer under the influence of a rotating magnetic field.
  • the magnetic field is generated by a magnet below the flask.
  • the floating magnetic stirrer may be used to cause both primary and secondary motion in the liquid, when used in combination with a Pearson flask.
  • the method contemplates the tilting of the flask, preferably at an angle of approximately 30° to the horizontal, so as to substantially increase the surface area of the liquid, thereby enhancing the contact of the cells with air and enhancing cell growth.
  • the herein disclosed method also contemplates the introduction into a flask of a buoyant, magnetic stirrer, including an impeller, the flask being either a Pearson flask, or a spherical or substantially spherical flask, preferably.
  • the advantages of the present invention apparatus and method are the elimination of all bearings, ease of cleaning, the elimination of the danger of crushing either cells or microcarriers, the increase of cell proliferation due to secondary motion, creating a suitable stirring action while leaving the liquid free from obstruction as occurs when a magnet is immersed in the liquid, and making full use of the viscous drag on the rotating liquid to generate the above noted secondary motion, thereby harnessing viscous drag to assist accomplishing the stirring of the liquid with the cells and microcarriers therein.
  • the herein disclosed apparatus has the advantage that any cap or top of the flask is completely free from any encumbrances, such as suspension elements, bearings, etc., and the cap can therefore be removed to provide access to the contents of the flask, so as to permit additions to the contents or withdrawal therefrom, without cessation or interference with the stirring action.
  • the present apparatus having the advantage of eliminating the necessity for such additional access openings in the flask.
  • a base housing 10 of conventional construction and including a motor 11 positioned with its axis vertical, and having connected to the shaft thereof a magnet assembly 12. Magnet assembly 12 will thereby be caused to rotate in a horizontal plane, beneath a seat 13 provided in the upper surface of the base housing 10.
  • Various controls may be provided, as is known in the art, for the actuating and stopping of the motor 11, as well as for controlling its speed of rotation.
  • a Pearson flask 15 of known construction, including a cylindrical side wall 16, the bottom of Pearson flask 15 having an upstanding conical portion 17 which tapers to a rounded apex 18, thereby forming an interior annular trough or channel 19.
  • the axis of the conical portion 17 lies on the central vertical axis 20 through the flask 15.
  • the bottom corners of the trough or channel 19 are radiused as shown at 21, so as to form a smooth joining of the vertical side walls and the horizontal bottom 22 of Pearson flask 15.
  • Pearson flask 15 is provided with a neck 23 having a cap 24 thereon, which may be of plain, unencumbered construction.
  • Access spouts 25 and 26 have caps 27 and 28, respectively, the spouts providing access, if needed, into the interior of the Pearson flask 15, so as to permit additions to or withdrawal of material thereinto.
  • These spouts and caps may be unnecessary, since access may be provided to the interior through the neck 23, without interfering with the stirring operation.
  • a suitable liquid 29 is contained in Pearson flask 15, having an upper surface 29a exposed to the atmosphere within Pearson flask 15.
  • the liquid 29 may be a cell culture medium, and if it is of the type designated as “anchorage dependent", there may be in the liquid 29 a large number of tiny solid beads, called microcarriers.
  • cultured cells which are “anchorage independent” do not require the utilization of such microcarriers, and the liquid 29 may be of either type of culture cells, included in a suitable nutrient liquid.
  • a buoyant stirrer 30 is provided in the flask 15, which. is preferably of the above noted Pearson flask type.
  • the stirrer 30 comprises a hermetically sealed envelope 31 of generally cylindrical shape having hemispherical ends 32.
  • the envelope 31 is of a material which is non-corrosive, and which will withstand exposure to wet steam at 123°C. Such materials are known in the art, and include Teflon, Tefzel, Kel-F, and Victrex, these being trademarks of various commercially available plastics.
  • Teflon, Tefzel, Kel-F, and Victrex these being trademarks of various commercially available plastics.
  • the ability to withstand steam of noted temperature insures that the stirrer 30 may be suitably sterilized.
  • a magnet 35 which is in the form of a bar, and may be made up of a plurality of bar magnets placed end to end. As shown in Fig. 3, a suitable adhesive 36 may be utilized to secure the magnet 35 to the interior wall of the envelope 31.
  • the density of the stirrer 30 is less than the density of the liquid 29, and is preferably approximately one half of the density of the liquid 29.
  • the bar magnet 35 housed within the envelope 31, has its axis generally parallel to the axis of the cylindrical portion of the envelope 31.
  • the length of the stirrer 31 is less than the diameter of the Pearson (or other) flask 15.
  • the magnetic field from the magnet assembly 12 will cause the stirrer 30 to rotate, generally on the axis 20 of the flask 15, due to magnetic coupling between the magnets of the magnet assembly 12 and the magnet(s) 35.
  • the magnetic field will prevent the stirrer 30 from engaging the walls of the Pearson or other flask 15, thereby avoiding crushing of the cells.
  • hydrodynamic forces will tend to keep the stirrer 30 centered in the Pearson or other flask 15, avoiding crushing of cells between the stirrer 30 and the walls 16 of flask 15.
  • stirrer 30 The stirring action of stirrer 30 on the liquid 29 will serve to keep all of the cells, and microcarriers, if present, in suspension, due to both the primary flow and the secondary flow or motion generated by the construction of the Pearson flask 15.
  • the buoyant stirrer 30, located at the top layers of the liquid 29, leaves the bulk of the liquid 29 free of all obstructions, thereby making full use of the viscous drag on the rotating liquid. This also assists in generating the above noted secondary motion which provides for the suspension of the cells and microcarriers, if present.
  • viscous drag is harnessed to stir and keep the cells and microcarriers, if present, in suspension.
  • the stirrer 40 comprises an envelope 41 having bulbous elements 42 at the ends thereof, and connected by a linear portion 43 of generally cylindrical configuration.
  • the bulbous elements are, of course, hollow and the envelope 41, as are all of the envelopes herein disclosed, is hermetically sealed.
  • the linear portion 43 may be of greater or lesser extent, providing a stirrer 40 of greater or lesser length.
  • a bar magnet 44 secured by suitable adhesive 45.
  • the bar magnet 44 is seen extending between the polar regions of the two bulbous elements 42, but may be of lesser length, in which case the bar magnet 44 may be adhered to other portions of the envelope 41.
  • Fig. 5 there is shown another embodiment of a stirrer designated 50, and having an envelope 51 with a pair of bulbous elements 52.
  • a very short linear portion 53 extends between the bulbous elements 52.
  • a bar magnet 54 is provided, extending (similar to the construction in Fig. 4) through the linear portion 53 and through the bulbous elements 52, being joined by adhesive 45 to the polar regions of the bulbous elements 52.
  • a stirrer 60 comprising a cylindrical, hollow body 61 of magnetically attractable material.
  • end caps 62 of any suitable material, secured or adhered to the ends of the body 61, so as to provide a hermetically sealed construction.
  • the body 61 being of magnetically attractable material, will be caused to rotate in the same manner as the stirrers hereinabove disclosed.
  • the stirrer 60 like the other stirrers, has a density less than the density of the liquid medium in which it is to be used, and so will float therein, as indicated by the line 63, which indicates the liquid surface.
  • the body 61 is preferably a hollow magnet.
  • a support 70 is provided for a vessel 80.
  • the support 70 may be a typical chemical laboratory stand, including a base 71, trunk 72, horizontal arm 73 and clamp 74 of known construction, for engaging and supporting the vessel 80.
  • the vessel 80 is of conventional construction, having cylindrical walls 81, and a bottom 82 perpendicular thereto, and with a neck 83 at its upper end, opposite the bottom 82.
  • the clamp 74 and the support 70 serve to position and hold the vessel 80 with its axis at an angle of 30° to the horizontal.
  • a suitable liquid 84 having a surface 84a.
  • the area of surface 84a when the vessel 80 is inclined as above noted, has an area approximately double the area of the surface when the vessel 80 is upright, with its axis vertical.
  • a buoyant, magnetic stirrer 30, 40, 50, 60 is contained within the vessel 80 and floats in the upper region of the liquid 84. It is rotated in the manner hereinabove described by the magnetic field of the magnet assembly 12, and will be maintained in position away from the wall 81 of vessel 80 so as to avoid crushing cells and microcarriers.
  • the enhanced surface area 84a of the liquid 84 facilitates gas absorption and allows more cells to come to the surface in a given time. This enhances the growth of the cells, accelerating cell production.
  • a base housing 110 having therein a rotating magnetic field generator 112, which include plurality of coil windings 114, 116 and 118, there being, a fourth coil winding not shown in Fig. 8. These four coil windings are connected magnetically to form two electromagnets at right angles to each other and the coils are connected to suitable circuit means 120, connected by conductor 122 to a suitable source of electricity in known manner.
  • the rotating magnetic field generator 112 is preferably made as provided in the article Direct Drive Magnetic Stirrers hereinabove referenced.
  • a generally spherical flask 125 is shown, having a neck opening 126; the flask 125 preferably has a rounded bottom, but, optionally, a portion of the bottom may be flattened. As shown, the flask 125 has a round bottom, and is supported in a cork ring 128.
  • a floating stirrer 130 which may comprise hollow, generally spherical elements 132 and 134. These may be made of a suitable plastic material, such as polypropylene. A suitable hole will have been made in each of the elements 132 and 134, and a bar magnet 136 inserted into the elements 132 and 134, and then the elements are secured together, in a hermetic fashion, thereby encasing the bar magnet 136 in a hermetically sealed, buoyant envelope.
  • the elements 132 and 134 may be more or less flattened at their abutting surface portions.
  • the buoyant magnetic stirrer 130 comprises, additionally, an impeller 140, for causing upward movement or secondary motion of liquid 129 within flask 124, in which the buoyant magnetic stirrer 130 floats.
  • the impeller 140 has, as shown in Fig. 9, four blades 142, 144, 146 and 148, although a greater or lesser number of blades may be utilized.
  • the blades 142-148 have a radial extent approximately equal to the length of the assemblage of the elements 132 and 134, and as will be understood, the entire stirrer 130 has dimensions so related to the neck opening 126 that it may pass therethrough.
  • the drawings will be understood to be generally descriptive, rather than dimensional.
  • a Pearson flask 155 generally of the type disclosed in Fig. 1, and the floating magnetic stirrer with impeller 130 is provided therein.
  • the Pearson flask will be seen to have an upstanding conical portion 157, similar to the portion 17, and otherwise generally be the same as and function in the same manner as the Pearson flask shown in Fig. 1.
  • the buoyant magnetic stirrer with impeller provides for superior performance, because of the enhancement of the secondary motion which is imparted to the culture medium, upon rotation of the stirrer under the impetus of the rotating magnetic field.
  • the buoyant magnetic stirrer may have different embodiments, including a plastic envelope housing one or more bar magnets, the envelope being cylindrical, with hemispherical end portions, or having bulbous elements at the ends, with a linear connecting portion.
  • the buoyant magnetic stirrer may be provided with an impeller, to provide an enhanced secondary motion of the culture medium.
  • the stirrer may be a cylindrical magnet, hollow and with end closures to provide buoyancy, all of the stirrers being of lesser density than the liquid, preferably having a density of approximately one-half of that of the liquid.
  • the herein disclosed buoyant magnetic stirrer may be utilized with a conventional flask, or with a Pearson flask, characterized by a conical projection at the bottom, forming an annular trough or channel in the bottom of the flask.
  • the present invention contemplates a method of stirring, using a buoyant stirrer, within a vessel having its axis either vertical, or tilted, preferably at 30° to the horizontal.
  • the herein disclosed apparatus and method avoid either submerged bearings or bearings in a cap, thereby avoiding both the damaging of cells and microcarriers, if present, and avoiding a cap with encumberances, making it difficult to clean.
  • the herein disclosed carrier is made of material enabling it to withstand sterilization by high temperature wet steam, and there may be enhanced, by the present invention stirrer apparatus and method, the secondary flow or motion and thereby enhancement of the suspension action of the cells in the medium. Where the axis of the vessel is tilted, enhanced exposure of the cells to atmosphere results.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Sustainable Development (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Mixers With Rotating Receptacles And Mixers With Vibration Mechanisms (AREA)

Claims (18)

1. Verfahren zum Aufrühren eines flüssigen Mediums, dadurch gekennzeichnet, daß das Medium in eine Flasche (18, 80, 125) gebracht wird, in der Flasche ein Rüher mit einem schwimmenden Stabmagneten (35, 44, 54, 61, 136) angebracht wird, die Flasche mit dem darin befindlichen Flüssigkeitsrüher nahe einer Einrichtung (12) zur Erzeugung eines magnetischen Drehfeldes angeordnet wird, so daß der Permanentmagnet sich in diesem Feld befindet, und daß die Drehfelderzeugungseinrichtung mit Energie versorgt wird, um den Rührer zu drehen, dessen Dichte geringer ist als diejenige des flüssigen Mediums.
2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß ein Gefäß oder eine Flasche (15, 80) vorgesehen wird, deren Seitenwände (16) gleiche Abstände von der Achse eines konischen Teils (17) derselben aufweisen, und daß das Gefäß oder die Flasche (15, 80) mit der Achse des konischen Teils (17) im wesentlichen senkrecht zur Drehebene des Magneten (35) angeordnet ist.
3. Verfahren nach Anspruch 1 oder 2, gekennzeichnet durch ein Flügelrad (140) zur Erzeugung einer nach oben gerichteten Strömung des flüssigen Mediums.
4. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß eine Flasche (80) vorgesehen wird und die Flasche zur horizontalen Lage hin geneigt wird, und daß ein Flügelrad (30, 40, 50, 60) vorgesehen wird, das in einer im wesentlichen horizontalen Ebene gedreht wird, während die Flasche (80 geneigt ist.
5. Verfahren nach Anspruch 4, dadurch gekennzeichnet, daß das Medium (86) in solcher Menge eingebracht wird, daß es die Flasche (80) teilweise füllt, so daß ein beträchtlicher Raum oberhalb des Flüssigkeitsspiegels bei der in geneigter Lage befindlichen Flasche verbleibt.
6. Verfahren nach Anspruch 5, dadurch gekennzeichnet, daß das flüssige Medium (84) in der Flasche aus einem Zellkulturmedium besteht.
7. Anlage zur Ausführung des Verfahrens nach einem der vorangehenden Ansprüche, mit einer Flasche, flüssigem Medium in der Flasche, einem Rührer in dem Medium und einer -Einrichtung zum Drehen des Rührers, dadurch gekennzeichnet, daß der Rührer ein schwimmender Stabmagnet (30, 40, 50, 60) ist, der eine geringere Dichte besitzt als die Dichte des flüssigen Mediums, wodurch der schwimmende Stabmagnet (30, 40, 50, 60) auf der Oberfläche der FLüssigkeit schwimmt und sich bei Betrieb um eine vertikale Achse in der Mitte der Flasche (15, 80, 125) dreht.
8. Anlage nach Anspruch 7, dadurch gekennzeichnet, daß die Dichte des Rührers etwa halb so groß ist wie die Dichte der Flüssigkeit.
9. Anlage nach Anspruch 7 oder 8, dadurch gekenzeichnet, daß die Flasche (15) zylindrische Wände, einen Boden (22) sowie eine eine Mulde (19) im Bodenteil der Flasche bildende Anordnung mit einem mittig angeordneten, nach oben stehenden konischen Teil aufweist.
10. Anlage nach Anspruch 7 oder 8, dadurch gekennzeichnet, daß die Flasche eine Längsachse aufweist, und daß eine Einrichtung (73, 74) die Flasche (15) mit ihrer Achse gegen die Vertikale geneigt hält.
11. Rührer zur Durchführung des Verfahrens nach einem der Ansprüche 1-6 zur Verwendung in einer Anlage nach einem der Ansprüche 7-10, mit einem Stabmagneten und einer schwimmenden Einrichtung zur Unterstützung des Stabmagneten in einer Menge von flüssigem Medium, wobei der Stabmagnet dadurch gekennzeichnet ist, daß er in einer Umhüllung (31,41) angeordnet ist, welche konvexe Ende (32) aufweist, und daß die Umhüllung (31, 41) zwei ausgebauchte Elemente (42, 52) aufweist, welche die konvexen Enden derselben umfassen.
12. Rührer nach Anspruch 11, dadurch gekennzeichnet, daß sich ein geradliniger Abschnitt (43, 53) zwischen den aufgebauchten Elementen (42, 52) erstreckt.
13. Rührer nach Anspruch 11 oder 12, dadurch gekennzeichnet, daß die aufgebauchten Elemente aus zwei kugelförmigen Elementen (132, 134) bestehen.
14. Rührer nach einem der Ansprüche 11 bis 13, gekennzeichnet durch ein Flügelrad (140) zur Erzeugung einer aufwärts gerichteten Strömung von flüssigem Medium in einer Flasche (125), in der der Rührer angeordnet ist.
15. Rührer nach Anspruch 14, gekennzeichnet durch ein Flügelrad (140) mit Schaufeln (142, 144, 146, 148) unterhalb der schwimmenden Einrichtung.
16. Rührer zum Aufrühren eines flüssigen Mediums in einem Gefäß, mit einem Stabmagneten (35, 44, 54, 61, 136), einer hermetisch abgedichteten, schwimmenden Umhüllung (31, 41, 51, 60, 136) zur Unterstützung des Stabmagneten in dem flüssigen Medium, wobei die schwimmende Umhüllung den Stabmagneten umgibt und aus Kunststoff besteht, der naßem Dampf bei 123°C widersteht, und wobei die Umhüllung (41, 51) aufgebauchte Enden (42, 52) aufweist.
17. Rührer nach Anspruch 16, dadurch gekennzeichnet, daß der Rührer ein Flügelrad (140) zur Erzeugung einer aufwärts gerichteten Strömung von flüssigem Medium in einer Flasche (125) aufweist, in welcher der Rührer angeordnet ist.
18. Rührer nach einem der Ansprüche 11 bis 17, dadurch gekennzeichnet, daß der Stabmagnet (61) ein Hohlmagnet ist.
EP83303260A 1982-06-09 1983-06-06 Schwimmender Magnetrührer für Kulturen Expired EP0105574B1 (de)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US38676482A 1982-06-09 1982-06-09
US386764 1982-06-09
US432128 1982-09-29
US06/432,128 US4498785A (en) 1982-06-09 1982-09-30 Floating magnetic stirrer for culture medium

Publications (3)

Publication Number Publication Date
EP0105574A2 EP0105574A2 (de) 1984-04-18
EP0105574A3 EP0105574A3 (en) 1984-06-06
EP0105574B1 true EP0105574B1 (de) 1990-01-10

Family

ID=27011586

Family Applications (1)

Application Number Title Priority Date Filing Date
EP83303260A Expired EP0105574B1 (de) 1982-06-09 1983-06-06 Schwimmender Magnetrührer für Kulturen

Country Status (5)

Country Link
US (1) US4498785A (de)
EP (1) EP0105574B1 (de)
JP (1) JPS5948071A (de)
DE (1) DE3381084D1 (de)
GB (1) GB2123706B (de)

Families Citing this family (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59206034A (ja) * 1983-05-09 1984-11-21 テクネ コーポレーション 浮游性磁気撹拌子を用いた撹拌装置および撹拌方法
US4465377A (en) * 1983-06-07 1984-08-14 Techne Corporation Magnetic stirrer apparatus with guided, floating stirrer
CH665217A5 (de) * 1985-02-15 1988-04-29 Agrogen Stiftung Verfahren und vorrichtung zur in vitro kultur von pflanzenzellen, pflanzengeweben, pflanzenorganen, pflanzenteilen sowie zur mikropropagation und regeneration von ganzen pflanzen.
US4759635A (en) * 1985-08-08 1988-07-26 Techne Corporation Magnetic stirrer apparatus with improved stirring action
GB2178971B (en) * 1985-08-08 1989-02-15 Techne Inc Magnetic stirrer apparatus with improved stirring action
ES2012391B3 (es) * 1986-03-10 1990-03-16 Solly Katz Dispensador de liquidos.
US4760028A (en) * 1986-07-25 1988-07-26 Techne Incorporated Bioreactor apparatus with surface aerator screen
US4836826A (en) * 1987-12-18 1989-06-06 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration Magnetic drive coupling
US5267791A (en) * 1991-12-13 1993-12-07 Corning Incorporated Suspended cell culture stirring vessel closure and apparatus
DE4403967C2 (de) * 1993-02-10 2002-04-18 Biosyntan Ges Fuer Bioorg Synt Verfahren und Vorrichtung zur Herstellung von Peptiden, Peptoiden und Oligonukleotiden und deren Verwendung
JP3349248B2 (ja) * 1994-03-22 2002-11-20 千寿製薬株式会社 流通型角膜透過実験器具およびこの実験器具を用いた実験装置
US6416215B1 (en) 1999-12-14 2002-07-09 University Of Kentucky Research Foundation Pumping or mixing system using a levitating magnetic element
US6758593B1 (en) * 2000-10-09 2004-07-06 Levtech, Inc. Pumping or mixing system using a levitating magnetic element, related system components, and related methods
CN1190486C (zh) * 2000-05-18 2005-02-23 周镭 菌体培养装置和方法及采用此类装置的菌体培养系统
US6733171B2 (en) * 2000-09-13 2004-05-11 Levitronix Llc Magnetic stirring apparatus and an agitating device
US8182137B2 (en) 2000-10-09 2012-05-22 Atmi Packaging, Inc. Mixing bag or vessel with a fluid-agitating element
US6837613B2 (en) * 2001-04-10 2005-01-04 Levtech, Inc. Sterile fluid pumping or mixing system and related method
US7086778B2 (en) * 2000-10-09 2006-08-08 Levtech, Inc. System using a levitating, rotating pumping or mixing element and related methods
US7762716B2 (en) * 2000-10-09 2010-07-27 Levtech, Inc. Mixing vessel with a fluid-agitating element supported by a roller bearing
WO2002045691A2 (en) * 2000-12-06 2002-06-13 Pharmacia Corporation Laboratory scale milling process
US7211430B2 (en) * 2001-08-03 2007-05-01 Becton, Dickinson And Company System for stirring growth medium
EP1534412B1 (de) * 2001-10-03 2010-08-18 Levtech Inc. Mischbehälter mit einer aufnahmevorrichtung für ein fluidbewegungselement
US20040131500A1 (en) * 2002-01-18 2004-07-08 Chow Herbert S. Device and method for evaluating platelets
US6908223B2 (en) 2002-04-12 2005-06-21 Hynetics Llc Systems for mixing liquid solutions and methods of manufacture
US6923567B2 (en) * 2002-04-12 2005-08-02 Hynetics Llc Mixing tank assembly
US6981794B2 (en) * 2002-04-12 2006-01-03 Hynetics Llc Methods for mixing solutions
US6988825B2 (en) * 2002-07-03 2006-01-24 Bio/Data Corporation Method and apparatus for using vertical magnetic stirring to produce turbulent and chaotic mixing in various states, without compromising components
US7153021B2 (en) * 2003-03-28 2006-12-26 Hyclone Laboratories, Inc. Container systems for mixing fluids with a magnetic stir bar
US20040248291A1 (en) * 2003-04-10 2004-12-09 Pentax Corporation Method for culturing cells, cell culture carriers and cell culture apparatus
CA2552717C (en) * 2004-01-07 2011-11-29 Levtech, Inc. Mixing bag with integral sparger and sensor receiver
EP2551676A1 (de) * 2005-03-28 2013-01-30 Becton, Dickinson and Company Vorrichtung und Verfahren zum Rühren von Teilchen in Suspension in einem flüssigen Medium
JP2007020387A (ja) * 2005-06-07 2007-01-25 Maguneo Giken:Kk 超伝導非接触回転装置
WO2008040567A1 (en) * 2006-10-03 2008-04-10 Artelis Flexible mixing bag, mixing device and mixing system
US20090130757A1 (en) * 2005-10-26 2009-05-21 Terentiev Alexandre N Bioreactor with mixer and sparger
EP1961806B1 (de) * 2006-05-13 2019-03-27 Pall Life Sciences Belgium Einweg-Bioreaktor
US20100157725A1 (en) * 2007-02-21 2010-06-24 Terentiev Alexandre N Roller Bearing for a Fluid-Agitating Element and Associated Vessel
US8110101B2 (en) 2007-08-30 2012-02-07 Veridex, Llc Method and apparatus for imaging target components in a biological sample using permanent magnets
US7828968B2 (en) * 2007-08-30 2010-11-09 Veridex, Llc Method and apparatus for imaging target components in a biological sample using permanent magnets
JP5685537B2 (ja) * 2008-09-05 2015-03-18 コーニンクレッカ フィリップス エヌ ヴェ クラスター・アッセイにおける改善した検出のための回転磁場
MX2013009620A (es) * 2011-02-25 2014-05-27 Algenol Biofuels Inc Sistema magneticamente acoplado para mezclado.
DE102011114191A1 (de) * 2011-09-22 2013-03-28 Eagleburgmann Germany Gmbh & Co. Kg Spalttopf für eine Magnetkupplung mit verbesserter Fluidströmung
US9339026B2 (en) 2012-06-14 2016-05-17 Therapeutic Proteins International, LLC Pneumatically agitated and aerated single-use bioreactor
CH707442A1 (de) * 2013-01-14 2014-07-15 Hochschule Rapperswil Inst Für Umwelt Und Verfahrenstechnik Vorrichtung zur Achsenstabilisierung von rotierenden Elementen.
US9790465B2 (en) 2013-04-30 2017-10-17 Corning Incorporated Spheroid cell culture well article and methods thereof
US20140334249A1 (en) * 2013-05-08 2014-11-13 Roxi Group, Inc. Beverage mixing, storing and dispensing apparatus
KR101609327B1 (ko) 2013-05-16 2016-04-08 유제형 교반 기능을 갖는 용기 시스템
CA2915507A1 (en) 2013-06-28 2014-12-31 Saint-Gobain Performance Plastics Corporation Mixing assemblies including magnetic impellers
US11944946B2 (en) 2013-06-28 2024-04-02 Saint-Gobain Performance Plastics Corporation Mixing assemblies including magnetic impellers
CN103638856B (zh) * 2013-12-04 2015-11-11 西北大学 磁子悬浮式磁力搅拌器
WO2015095892A1 (en) * 2013-12-20 2015-06-25 Pbs Biotech, Inc. Vertical mixing bioreactor and drive system therefor
JP2017532971A (ja) 2014-10-29 2017-11-09 コーニング インコーポレイテッド 細胞培養集合体を生成するためのマイクロウェル設計および製造
KR102460969B1 (ko) 2014-10-29 2022-10-31 코닝 인코포레이티드 세포 배양 인서트
US10583409B2 (en) * 2016-03-31 2020-03-10 General Electric Company Axial flux stator
US11097236B2 (en) 2016-03-31 2021-08-24 Global Life Sciences Solutions Usa Llc Magnetic mixers
CN106282013B (zh) * 2016-09-09 2018-06-01 东北农业大学 一种便于微生物紫外线诱变的装置
US9873097B1 (en) 2017-07-12 2018-01-23 Boris Dushine Magnetic stirring system for wine aeration and method of using same
CN111051494B (zh) 2017-07-14 2024-03-29 康宁股份有限公司 用于手动或自动培养基交换的3d细胞培养容器
US11857970B2 (en) 2017-07-14 2024-01-02 Corning Incorporated Cell culture vessel
US10881135B1 (en) 2017-11-10 2021-01-05 Creative Destruction, LLC Cyclonically cooled and filtered smoking water pipe and method
CN112533691A (zh) * 2018-05-22 2021-03-19 科学之门有限公司 无线感测封闭环境的性质及其装置
US11912968B2 (en) 2018-07-13 2024-02-27 Corning Incorporated Microcavity dishes with sidewall including liquid medium delivery surface
JP7171696B2 (ja) 2018-07-13 2022-11-15 コーニング インコーポレイテッド 相互接続されたウェルを有するマイクロプレートを備えた流体デバイス
EP3649229B1 (de) * 2018-07-13 2021-08-25 Corning Incorporated Zellkulturgefässe mit stabilisatorvorrichtungen
US10220361B1 (en) 2018-08-03 2019-03-05 Boris Dushine Magnetic stirring system for the automated and optimized reconstitution of powdered infant formulations and methods of using same
US10350561B1 (en) 2018-08-03 2019-07-16 Boris Dushine Magnetic stirring system for wine aeration and method of using same
CN109550451B (zh) * 2018-09-30 2021-03-12 中国水利水电科学研究院 一种节能高效的脱硫用制浆装置
TWI809833B (zh) * 2022-04-22 2023-07-21 牟敦剛 磁性耦合方法以及磁性耦合攪動及其裝置

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2036076A (en) * 1934-09-22 1936-03-31 Carl A Philippl Toy or game
US2350534A (en) * 1942-10-05 1944-06-06 Rosinger Arthur Magnetic stirrer
US2770073A (en) * 1954-06-21 1956-11-13 William J Sullivan Animated display device
US3172645A (en) * 1961-07-21 1965-03-09 Doryce Appleton Agitator for foods of a liquid form containing solids
US3245665A (en) * 1964-03-18 1966-04-12 Arthur H Thomas Company Magnetic mixing bar
DE2444328A1 (de) * 1974-09-17 1976-03-25 Wolfgang Gruhn Verfahren zur bewegung von fluessigkeiten, gasen, granulaten oder staeuben, sowie zum antrieb leistungsarmer geraete mittels elektromagnetisch fererregter rotationsoder schwingkoerper
JPS55147143A (en) * 1979-03-29 1980-11-15 Toyo Eng Corp Agitation method
GB2053704A (en) * 1979-07-17 1981-02-11 Techne Cambridge Ltd A flask for use in stirring particles in suspension such as microcarriers for anchorage-dependent living cells in a liquid culture medium
GB2062481A (en) * 1979-11-07 1981-05-28 Techne Cambridge Ltd Stirring apparatus
GB2082930B (en) * 1980-08-27 1984-02-22 Thomas Thomas Ronald Magnetic stirring element
JPS6010775B2 (ja) * 1982-01-06 1985-03-20 正信 井口 磁気撹拌機における回転撹拌用浮遊磁性体

Also Published As

Publication number Publication date
DE3381084D1 (de) 1990-02-15
GB8315883D0 (en) 1983-07-13
GB2123706B (en) 1986-09-03
EP0105574A2 (de) 1984-04-18
JPS5948071A (ja) 1984-03-19
US4498785A (en) 1985-02-12
EP0105574A3 (en) 1984-06-06
GB2123706A (en) 1984-02-08

Similar Documents

Publication Publication Date Title
US4498785A (en) Floating magnetic stirrer for culture medium
US4759635A (en) Magnetic stirrer apparatus with improved stirring action
JPS60160882A (ja) 発酵および組織培養容器用に適した撹拌器
US3854704A (en) Magnetic cell stirrer
US20100041095A1 (en) Pneumatic bioreactor
US4465377A (en) Magnetic stirrer apparatus with guided, floating stirrer
US10081787B2 (en) Vertical wheel bioreactors
US4450076A (en) Small-sample dialyzer
US4382685A (en) Method and apparatus for stirring particles in suspension such as microcarriers for anchorage-dependent living cells in a liquid culture medium
US4162855A (en) Magnetic stirrer apparatus
US3900186A (en) Magnetic cell stirrer
US6109780A (en) Dynamic vortex impeller
US20030053371A1 (en) Magnetic stirring apparatus and an agitating device
US4760028A (en) Bioreactor apparatus with surface aerator screen
JP2004534544A (ja) 使い捨て容器
EP0053869B1 (de) Verfahren und Vorrichtung zum Rühren von Teilchen in Suspension wie Mikroträgern für Verankerungsabhängige lebende Zellen in einem flüssigen Kulturmedium
US5846817A (en) Bioreactor, in particular for microgravity
JP2005151812A (ja) 浮遊攪拌培養装置
EP0124970A2 (de) Magnetrührer und Rührverfahren
WO1998006485A1 (en) Agitation apparatus
JP2005013112A (ja) 浮遊攪拌培養装置
JPS6221312Y2 (de)
JPH06261747A (ja) 細胞の液体培養方法及び培養装置
GB2178971A (en) Floating magnetic stirrer for culture medium
JPH0347068A (ja) 植物組織培養槽

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

PUAL Search report despatched

Free format text: ORIGINAL CODE: 0009013

AK Designated contracting states

Designated state(s): DE FR GB

AK Designated contracting states

Designated state(s): DE FR GB

17P Request for examination filed

Effective date: 19841204

RBV Designated contracting states (corrected)

Designated state(s): DE FR

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): DE FR

REF Corresponds to:

Ref document number: 3381084

Country of ref document: DE

Date of ref document: 19900215

ET Fr: translation filed
PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 19900613

Year of fee payment: 8

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 19900629

Year of fee payment: 8

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed
PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FR

Effective date: 19920228

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Effective date: 19920401

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST